OBJECTIVE: To assess how subjective tolerability to medication compares in patients taking ziprasidone or haloperidol for acute schizophrenia. METHODS: A 6-week parallel-group, open-label study randomly assigned 555 patients with acute schizophrenia to sequential IM/oral ziprasidone (<40 mg IM for <3 days, 40 to 80 mg oral thereafter) or haloperidol (<10 mg IM for <3 days, 5 to 20 mg oral thereafter). A 10-question Drug Attitude Inventory (DAI) was administered at randomization (baseline), Days 1-3, Week 1, and Week 6 or endpoint. Primary outcome was DAI total score by visit and change from baseline. Additional outcomes were DAI subjective positive score, subjective total score, and attitudes/values score. Factor loading and standardized discriminant coefficients were applied. Inferential analyses were based on main effects ANCOVA. RESULTS: Patients in the ziprasidone group exhibited statistically significant improvement in subjective tolerability over patients in the haloperidol group, as measured by DAI scores: total score after Week 1 (P<0.01), subjective positive score after Week 1 (P<0.01), and subjective total scores after IM therapy (P<0.05) and Week 1 (P<0.001). CONCLUSIONS: Patients with acute schizophrenia manifest better feelings about using ziprasidone than haloperidol, especially at treatment outset (IM phase through transition to oral dosing). These findings have implications for better patient management during acute exacerbations, for smooth transition from IM to oral treatment, and for improved compliance with long-term ziprasidone therapy.